An Immobilization Method of Chiral Quaternary Ammonium Salts onto Polymer Supports
An Immobilization Method of Chiral Quaternary Ammonium Salts onto Polymer Supports
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DOI：
10.1002/anie.200802800
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Itsuno, Shinichi
中科院分区：
文献类型：
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作者：
Arakawa, Yukihiro;Haraguchi, Naoki;Itsuno, Shinichi
手性季铵盐作为有机催化剂的不对称转化反应已被广泛研究。自1984年默克公司的一个研究小组的开创性工作以来，[1]金鸡纳生物碱衍生的季铵盐已被广泛用作各种不对称反应的手性有机催化剂。[2]甘氨酸希夫碱在对映体纯季铵盐存在下的不对称烷基化反应是手性α-氨基酸的典型不对称合成。[3]从反应效率的观点来看，聚合物固载的手性催化剂已被用于不对称反应，在有机合成中引起了相当大的兴趣。虽然人们已经开发了许多聚合物固载的手性催化剂，但迄今为止，关于聚合物固载的手性季铵盐的报道还很有限。[4]Chiellini和Solaro在1977年[5]和科隆纳等人在1978年报道了第一个例子。[6]1981年，小林和岩井报道了固定在聚苯乙烯上的喹啉盐的不对称催化作用。[7]霍奇埃塔尔。也报道了聚合物固定的金鸡纳生物碱的季铵盐[8]，其中聚合物简单地通过用部分氯甲基化的交联聚苯乙烯季铵化金鸡纳生物碱来制备。纳杰拉及其同事使用相同类型的聚合金鸡纳生物碱季铵盐用于N-二苯基亚甲基甘氨酸酯的对映选择性烷基化。[9]Cahard及其同事开发了一种类似类型的具有间隔臂的聚苯乙烯固定化手性季铵盐。[10]此外，将氢化辛可尼丁盐固定到梅里菲尔德树脂上并用于相同的烷基化反应。[11]聚（乙二醇）也被用作手性季铵盐的聚合物载体。[12-14]上述所有实例均涉及聚合物与手性季铵盐之间的共价键。我们发现，磺酸季铵盐是相当稳定的，具有磺酸基团的聚合物可以通过离子键取代季铵盐阳离子。[15]据我们所知，这是一种新型的固定化，包括手性催化剂和聚合物之间的离子键。我们已经开发了两种方法的离子固定：第一个涉及的聚合的手性季铵磺酸盐单体，第二个是固定的手性季铵盐到磺化聚合物通过离子交换反应。这些高分子手性季铵盐被成功地用作高分子有机催化剂在甘氨酸衍生物的不对称烷基化。这是通过离子相互作用固定季铵盐的第一个例子。由于手性季铵磺酸盐可以很容易地从辛可尼定制备，我们已经从这种底物制备了我们的苯乙烯磺酸盐单体（方案1）。将N-苄基辛可尼啶鎓氯化物（1a）与对苯乙烯磺酸钠（2b）在水中反应，随后用二氯甲烷萃取，得到手性季铵单体3b。该手性单体与苯乙烯、二乙烯基苯在自由基条件下进行共聚，得到相应的聚合物手性季铵盐4 aA。通过使用该方法，任何类型的手性季铵盐都可以转化为相应的单体。与传统的共价键合方法相比，该方法是一种更容易获得手性季铵盐聚合物的方法。通过这个...
Asymmetric transformations by means of a chiral quaternary ammonium salt acting as the organocatalyst have been extensively studied. Since the pioneering work by a research group at Merck in 1984,[1] cinchona-alkaloid-derived quaternary ammonium salts have been widely used as chiral organocatalyst in various asymmetric reactions.[2] The enantioselective alkylation of glycinate Shiff base in the presence of an enantiopure quaternary ammonium salt is a typical asymmetric synthesis of chiral α-amino acids.[3] From the viewpoint of reaction efficiency, polymer-immobilized chiral catalysts which have been used for asymmetric reactions are of considerable interest in organic synthesis. Although numerous polymer-immobilized chiral catalysts have been developed, but so far, there have been limited reports on polymer-immobilized chiral quaternary ammonium salts.[4] First examples were reported by Chiellini and Solaro in 1977 [5] and Colonna et al. in 1978.[6] In 1981, Kobayashi and Iwai reported asymmetric catalysis by quinium salts immobilized onto polystyrene.[7] Hodge etal. also reported the quaternary ammonium salts of polymer-immobilized cinchona alkaloids [8] where the polymers were simply prepared through quaternarization of the cinchona alkaloid with partially chloromethylated cross-linked polystyrene. Najera and co-workers used the same type of polymeric cinchonaalkaloid quaternary ammonium salt for the enantioselective alkylation of N-diphenylmethylene glycine esters.[9] Cahard and co-workers have developed a similar type of polystyreneimmobilized chiral quaternary ammonium salts that have a spacer arm.[10] Furthermore, hydrocinchonidinium salts were immobilized onto Merrifield resin and used for the same alkylation reaction.[11] Poly (ethylene glycol) was also utilized as a polymer support of a chiral quaternary ammonium salt.[12–14] All of the above examples involve a covalent bond between the polymer and the chiral quaternary ammonium salt. We have found that quaternary ammonium sulfonate is quite stable and that polymers possessing sulfonate groups can immobilize quaternary ammonium cations through ionic bonding.[15] To our knowledge, this is a new type of immobilization comprising of an ionic bond between a chiral catalyst and a polymer. We have developed two methods of the ionic immobilization: the first involves the polymerization of a chiral quaternary ammonium sulfonate monomer, and the second is the immobilization of a chiral quaternary ammonium salt onto a sulfonated polymer through an ion exchange reaction. These polymeric chiral quaternary ammonium salts were successfully used as polymeric organocatalysts in the asymmetric alkylation of a glycine derivative. This is the first example of the immobilization of quaternary ammonium salt through an ionic interaction.As chiral quaternary ammonium sulfonates can be easily prepared from cinchonidine, we have prepared our styrene sulfonate monomers from this substrate (Scheme1). N-Benzylcinchonidinium chloride (1a) was treated with sodium p-styrene sulfonate (2b) in water, and subsequent extraction with dichloromethane gave the chiral quaternary ammonium monomer 3b. The chiral monomer was copolymerized with styrene and divinylbenzene under radical condition to give the corresponding polymeric chiral quaternary ammonium salt 4 aA. By using this method, any type of chiral quaternary ammonium salt can be transformed into its corresponding monomer. This method is an easier way to obtain the chiral quaternary ammonium salt polymers in comparison to the conventional covalent bonding method. By means of this …